Systemic biomarkers of retinopathy of prematurity in preterm babies

Abstract

Purpose Retinopathy of prematurity (ROP) progression is an inter-play of various perinatal and neonatal angiogenic and inflammatory cytokines . A small subset of ROP progresses to ROP requiring treatment. The present study was conducted with the aim to determine whether levels of IL-6, IL-8 and VEGF in serum and urine at the time of first ROP screening visit could be a biomarker for the prediction of development of treatable ROP. Method Prospective single-center observational study of preterm babies screened for ROP. Blood and urine samples were collected as a part of routine sampling at initial ROP screening visit and stored at −80 °C for further processing. The babies were followed up and grouped into ‘Group A’ comprising of 35 babies who developed treatable ROP and ‘Group B’ comprising of 36 babies with regressed ROP or no ROP. The evaluation of blood and urine samples was done for IL6, IL8 and VEGF by solid-phase sandwich RayBio® Human ELISA kit. Results The median serum values for IL-6, IL-8 and VEGF in Group A and Group B were 5.8 pg/ml (IQR 1.5,128.5) and 8.7 pg/ml (IQR 1.5,30.5), 55.9 pg/ml (IQR 28.0, 392.9) and 27.0 pg/ml (IQR 20.5,444.9) and 26.6 pg/ml (IQR 6.3, 39.4) and 30.0 pg/ml (IQR9.2,70.3), respectively. Group A had significantly increased levels of IL-8 ( p < 0.05). However, AUROC curve for serum IL-8 demonstrated suboptimal discriminating ability. Conclusion Babies developing ROP requiring treatment had significantly increased levels of IL-8 in the serum at the time of initial screening. However, it could not serve as predictor for treatable ROP.

Early detection and correlation of tear fluid inflammatory factors that influence angiogenesis in premature infants with and without retinopathy of prematurity

“…However, other studies have reported no significant differences in the level of the vitreous humor of RANTES-CCL5 between controls and ROP infants,[ 21 ] decreased levels in serum,[ 48 ] and blood[ 49 ] of ROP infants. An increased IL-8 level in the tear fluid of ROP infants in the current is supported by reports that have also shown an increase in the IL-8 levels in the vitreous humor,[ 21 ] aqueous humor,[ 50 ] tear fluid,[ 21 ] serum,[ 51 ] and blood[ 52 ] of ROP infants. A study reported that the levels of IL-8 in the urine were not significantly different between control pre-term infants and ROP infants.…”

“…A study reported that the levels of IL-8 in the urine were not significantly different between control pre-term infants and ROP infants. [ 51 ] Studies have also reported conflicting observations with reference to the levels of IL-8 in amniotic fluid, with one study demonstrating a significant increase[ 53 ] and the other with no significant difference[ 54 ] between controls and ROP infants. Various reports have also shown differences in the observation with reference to IL-6 and MCP1-CCL2 levels in ROP infants.…”

Systemic Cytokines in Retinopathy of Prematurity

“…In a rat OIR model, increased expression of an IL-8 homologue was noted during the peak time points of neovascularization [ 38 ]. Accordingly, a few studies have also demonstrated the correlation between high plasma/serum IL-8 levels in preterm infants after birth and the later development of severe ROP [ 30 , 39 , 40 ].…”

“…Nonetheless, published data remained inconclusive regarding the systemic levels of VEGF in association with ROP. Among preterm neonates who eventually developed ROP, some researchers found that VEGF concentrations in the early period of life in cord blood at birth and circulating blood are significantly lower than those in their non-ROP counterparts [ 72 , 85 , 86 ], while some observed the opposite results [ 87 , 88 , 89 ] and others found no difference [ 40 , 58 , 90 ].…”

Ranibizumab for the treatment of retinopathy of prematurity: systematic review and meta-analysis

“…The retina of newborns is underdeveloped and has an avascular zone. The pathology has two phases: first, it has an avascular zone owing to hyperoxia or fluctuating oxygen levels, and second, the avascular zone of retina results in a high concentration of vascular endothelial growth factor (VEGF), which promotes the formation of abnormal vasculature (5). The medication used for intravitreal injections include ranibizumab and bevacizumab (6), which are anti-VEGF, both have shown low prevalence of developing refractive errors in the future although bevacizumab-treated eyes in severe cases of ROP were linked to a higher likelihood of myopia or neurodevelopmental damage (7).…”